期刊
JOURNAL OF NEUROCHEMISTRY
卷 85, 期 2, 页码 299-305出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1471-4159.2003.01657.x
关键词
behavior; exercise; GDNF; neurotrophic factor; Parkinson's disease; striatum
资金
- NIMH NIH HHS [MH29670] Funding Source: Medline
- NINDS NIH HHS [NS23979, NS19608, NS07433] Funding Source: Medline
Unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) causes a loss of dopamine (DA) in the ipsilateral striatum and contralateral motor deficits. However, if a cast is placed on the ipsilateral limb during the first 7 days following 6-OHDA infusion, forcing the animal to use its contralateral limb, both the behavioral and neurochemical deficits are reduced. Here, we examine the effect of forced reliance on a forelimb during the 7 days prior to ipsilateral infusion of 6-OHDA on the deficits characteristic of this lesion model. Casted animals displayed no behavioral asymmetries as measured 14-28 days postlesion and a marked attenuation in the loss of striatal DA and its metabolites at 30 days. In addition, animals receiving a unilateral cast alone had an increase in glial cell-line derived neurotrophic factor (GDNF) protein in the striatum corresponding to the overused limb. GDNF increased within 1 day after the onset of casting, peaked at 3 days, and returned to baseline within 7 days. These results suggest that preinjury forced limb-use can prevent the behavioral and neurochemical deficits to the subsequent administration of 6-OHDA and that this may be due in part to neuroprotective effects of GDNF.
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